And when another gay-rights measure came up in 2010 — repealing the “don’t ask, don’t tell” ban on LGBT individuals from serving openly in the military — North Carolina GOP Sen. Richard Burr joined Democrats to kill the long-standing policy.

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Cory Booker officiates same-sex marriage

But when it comes to the ENDA bill heading to the Senate floor as soon as next week, those GOP senators aren’t so sure. They are balancing growing public acceptance of gay rights against concerns that the bill — which includes provisions addressing gender identity — is too expansive and doesn’t do enough to protect religious institutions.

“I said when I did ‘don’t ask, don’t tell’ don’t misinterpret this as a blank check on issues that relate to same-sex anything,” Burr told POLITICO.

With the Senate poised to consider perhaps the most significant gay rights measure since the repeal of “don’t ask, don’t tell,” a handful of Republican senators will help determine its fate. While the bill has the support of every Senate Democrat, just four out of 44 Republican senators have yet to endorse the measure — a sign of how the party is still trying to appeal to a new bloc of voters who are becoming more open to gay rights.

“It’s significantly broadened [from the 2007 House bill], and with that comes greater possibilities for litigation and compliance costs,” Flake said. “I’m a firm ‘no’ if it’s the Senate bill.”

But supporters of the measure say those concerns are misplaced. And with Republicans in Congress still overwhelmingly opposed to gay marriage despite growing public approval of the issue, GOP backers of the ENDA bill argue that supporting the measure would help broaden the party’s appeal to young and LGBT voters who have been turned off by social conservative policies.

“I believe that if we’re to be a majority party, “that we have to be a growing party, rather than a narrowing party,” said former Sen. Norm Coleman (R-Minn.).

Coleman added, “Some of us aren’t there on marriage equity, but there’s no reason we shouldn’t be there on nondiscrimination. We’re the party of Lincoln. It’s our roots.”

The Employment Non-Discrimination Act of 2013 would address discrimination in the workplace by making it illegal to fire, refuse to hire or refuse to promote employees based on their sexual orientation or gender identity. It is crafted to mirror Title VII of the Civil Rights Act, though it provides what proponents call a “broad” religious exemption.

Cory Booker, who will be sworn in Thursday as New Jersey’s new Democratic senator, will provide Democrats with 55 votes in support of ENDA. That puts the bill tantalizingly close to the 60 votes needed to overcome a filibuster. Two GOP senators are backing the plan — Sens. Mark Kirk of Illinois and Susan Collins of Maine. And two other GOP senators — Lisa Murkowski of Alaska and Orrin Hatch of Utah — voted for the plan during a committee session in July, though Hatch said he wanted to see other changes to the bill before supporting it on the floor.

On top of that, the American Unity Fund, founded by major GOP donor Paul Singer, has hired two former GOP lawmakers as lobbyists — Coleman and former New York Rep. Tom Reynolds — to press Republicans to back the plan. Reynolds is making clear that this issue isn’t the same as gay marriage — an issue he opposed when he served in Congress — saying the bill eliminates only “workplace discrimination.”

A prime target for backers of the bill is Ohio Sen. Rob Portman, who became the first sitting GOP senator to back same-sex marriage earlier this year after learning his college-age son is gay.

In an interview Wednesday, Portman said he is still “undecided” on how to vote, saying he was having “constructive” conversations about “doing everything we can to protect religious liberty” provisions in the bill.

“I have always strongly believed that we should not discriminate against people based on who they are,” Portman said when asked whether it would be hard to oppose the measure after backing gay marriage. “In other words, because one of my constituents was gay, he or she should not be fired. And I’m fine with that.”

Proponents of the measure say it’s time for the federal government to catch up as 17 states, the District of Columbia, and hundreds of local governments have laws on the books to prevent workplace discrimination against gays and lesbians. A wide array of Fortune 500 companies have also adopted such policies. And polls show that an overwhelming majority of the American public not only supports the proposal but also believes such laws are already on the books.

Democratic leaders are bullish about their prospects, particularly since there hasn’t been much opposition among outside groups to the measure. The U.S. Chamber of Commerce is remaining neutral on the bill. The Family Research Council has voiced opposition, though not as aggressively as on other issues. And a spokesman for the conservative group Heritage Action said it had “serious concerns” with the bill but did not elaborate.

Sen. Jeff Merkley (D-Ore.), a lead sponsor of the bill, is trying to alleviate GOP senators’ concerns. He has buttonholed GOP senators like Dean Heller of Nevada, who is still on the fence on whether to back the measure, saying he wants to make sure the bill isn’t too restrictive on states implementing their own laws.

Other GOP senators are taking their concerns over states’ rights even further. Sen. Lamar Alexander (R-Tenn.), a bipartisan deal-maker who faces a primary challenge in his 2014 reelection bid, said the bill amounted to “too much federal overreach.”

McCain, the Arizona Republican and 2008 GOP presidential nominee, said he has concerns about whether the bill imposes quotas, could prompt reverse discrimination and have other negative unforeseen consequences.

Asked if opposing the bill would hurt the party’s ability to reach out to younger voters, McCain said: “I think the young people and old do not believe in reverse discrimination, they don’t believe in quotas, and they don’t believe that some of the programs that we saw in the name of racial equality implemented in the past which turned out to be counterproductive.”

McCain added: “Ask people in Boston if busing was a good idea.”

But supporters say those concerns won’t come to pass. And politically, they say, it would only cause the GOP — which is suffering rock-bottom approval ratings — even greater harm if it were to block it, much like the recent fight over the Violence Against Women Act.

“The times they are a-changing,” said New York Sen. Chuck Schumer, the chamber’s No. 3 Democrat. “If you want to alienate young voters, opposing this is a good way to do it. And they know that.”